--***BBS2001 Summary Part 2
Case 4- Toxicology
Its britney bitch
Toxicology… toxic… britney. I couldn’t help myself I’m sorry.
How does the body respond to particulate matter substances?
Learning Goals
- What are particulate matter compounds, their classification, composition and our exposure to
them
- Pharmacokinetic rules, distribution, how PM doesn’t follow that
- What is ROS (do not look at different forms of DNA damage) shortly address different types,
what are our defence mechanism. How long does the lung cope with this toxicity, anti oxidants,
what is oxidative stress
Keywords
- Particles/particulate matter (Size, distribution, exposure)
- ROS
- Antioxidants
- Inflammation
- Oxidative stress
, - Genotoxicity (primary and secondary)
Particulate matter (PM) is the term for a mixture of solid particles and liquid droplets found in the air.
Some particles, such as dust, dirt, soot, or smoke, are large or dark enough to be seen with the naked
eye. Others are so small they can only be detected using a big fancy electron microscope.
They are emitted from vehicles, factories, construction sites, tilled fields, unpaved roads, and burning of
fossil fuels. It is also formed by grilling food on charcoal or gas grills, burning leaves and brush, smoking
cigarettes, and burning wood in a fireplace or stove.
Size
PM is usually measured in 4 size ranges: PM10 , PM2.5, PM1 and PM<0.1
PM10 refers to particles with diameters that are less than or equal to 10 microns in size (a micron, or
micrometer, is one-millionth of a meter).
PM2.5, also called "fine particulates," consists of particles with diameters that are less than or equal to
2.5 microns in size. PM2.5 is a more serious health concern than PM10, since smaller particles can
travel into the mid section of our lungs and cause more harmful effects.
PM1 Can travel into the deepest section of our lungs
PM<0.1 can not only get to the deep dark depths of our lungs, but can potentially cross over into our
bloodstream, causing the worst health effects of any of the particulates.
Defence Mechanisms
The respiratory system has defense mechanisms to clean and protect itself thus only extremely small
particles can penetrate deep to the lung.
The walls of the alveoli have type II alveolar cells scattered between type I alveolar cells. They secrete
surfactant (detergent substance). Surfactant coats the alveolar surface. Also, alveolar macrophages
ingest pathogens and nanoparticles.
The larger particles will be captured in the upper parts of the nasopharyngeal tract and can be removed
by coughing or remain there and form a sedimentation layer of the epithelium.
The alveolar macrophages can’t remove a nanoparticle if it’s too small and the smallest of the particles
can pass to the bloodstream and cross the barrier.
,Exposure
We become exposed to particulates when breathing in polluted air or second hand smoke. PM can
cause or aggravate cardiovascular and lung diseases, heart attacks and arrhythmias. It can also affect the
central nervous system and the reproductive system, and can cause cancer.
Combustion of fossil fuels such as coal, oil, and petrol can produce
- coarse particles from the release of non-combustible materials such as fly ash,
- fine particles from the condensation of materials vaporized during combustion,
- secondary particles through the atmospheric reactions of sulphur oxides and nitrogen oxides
initially released as gases.
Distribution
, PM levels are going to be higher in cities that have more traffic. LA has more traffic than NYC because it
has less of a public transport system and is more spread out. This means people have to use cars to drive
around, hence the super duper high PM rate.
Pharmacodynamics
This is called Antibiotic pharmacokinetics. It refers to how (and to what extent) antibiotics enter the
body, where they go once they are “inside,” and how they get out. These three phases of
pharmacokinetics are described as absorption, distribution, and metabolism/excretion. This often gets
shortened to ADME.
- Absorption
- How is the medication absorbed (through the skin, the intestine, the mouth)?
- For particulate matter this could be:
- Passive diffusion
- Carrier mediated transport
- Facilitated diffusion
- Phagocytosis and pinocytosis
- Distribution
- How does it spread to the different tissues?
- The concentration in tissues can be very different to the conc found in the blood,
making it unpredictable as to what effect it will have on the body.
- The extent to which drugs spread is dependent on their physicochemical properties
- Also depends on patient- blood flow and obesity can affect dosage
- There are limits to this for toxins! For example:
- Binding to plasma protein
- Distribution to storage site
